Fioricet

In the past Fioricet was not a controlled substance whereas Fiorinal was.(CIII)

The reason for this was Fiorinal contains aspirin and Fioricet contains acetaminophen.

Aspirin is highly bound to plasma proteins whereas acetaminophen is not.

Aspirin being bound to these proteins allows for a higher blood level of Butalbital.

Butalbital is metabolized to Phenobarbital therefore more free Butalbital leads to greater potential for abuse.

Fioricet
Combination of
Butalbital Barbiturate
Acetaminophen Miscellaneous Analgesic
Caffeine Xanthine
Clinical data
Trade names Fioricet
AHFS/Drugs.com fioricet
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Oral
Legal status
Legal status
  • prescription
Generic Fioricet (50/40/325)

Fioricet and Esgic are brand names of a combination of butalbital (a barbiturate), acetaminophen and caffeine which is indicated for the treatment of tension headaches, muscle contraction headaches and post-dural puncture headaches. Although not indicated, they are commonly used to treat migraines and other pain related ailments.

Medical uses

Fioricet is indicated for the treatment of muscle tension or muscle contraction headaches. It is also commonly prescribed for migraines although it is not FDA indicated for this use in the United States. The usual adult dose is 1-2 tablets every four hours as needed, not exceeding six tablets in a 24-hour period.[1][2]

Side effects

Commonly reported side effects for Fioricet include:

Fioricet is implicated as causing repeat headaches with over-use.[3]

Rare side-effects

Overdose

The treatment of Fioricet overdose is complicated by the presence of two substances which are highly toxic when taken in excessive amounts. Fioricet overdoses generally result in toxic amounts of both acetaminophen and butalbital being consumed at once, requiring both overdoses to be treated at once. Fioricet overdose by anyone and/or any consumption by persons to whom it is not prescribed (particularly children) is always a medical emergency and medical attention must be sought immediately if an overdose or consumption by other persons is suspected. Fioricet overdose is often fatal and symptoms may not present for hours following consumption; once initial overdose symptoms present they can progress rapidly and there may not be time to reach appropriate medical care after this point.

Acetaminophen exerts its toxicity through the production of a toxic metabolite which can sometimes produce liver damage with doses as low as 4,000 mg, although normally requiring doses that are much higher. Acute liver failure may result in doses greatly exceeding this, and death has been known to occur with ingestion of 10,000-15,000 mg (10-15 grams of pure acetaminophen). The specific antidote to acetaminophen overdose is N-acetylcysteine. Acute renal failure and upper gastrointestinal bleeding may also occur.

Butalbital exerts its toxicity through excessive sedation resulting in respiratory depression and ultimately death via hypoxia. Nonlethal overdoses may also result in coma and death. There is no specific antidote to barbiturate overdose and treatment is supportive. Common treatment regimens generally include the administration of intravenous administration of saline, naloxone, thiamine, glucose, sodium bicarbonate to alkalize the urine to increase rate of excretion, and activated charcoal via nasogastric tube. It is not uncommon for a doctor to recommend observation of the patient in the emergency department for a number of hours or admission to the hospital for several days of observation if symptoms are severe and to counsel the patient on drug abuse or refer them for psychiatric evaluation.

Mechanism of action

Butalbital has generalized depressant effect on central nervous system and, in very high doses, has peripheral effects. Acetaminophen has analgesic and antipyretic effects mediated by a metabolite which acts at cannabinoid receptors, contrary to popular belief it is not an antiinflammatory at safe levels (it becomes toxic at doses above 1,000mg per dose and/or 3,000mg per day). Caffeine is thought to produce constriction of cerebral blood vessels and serves to counteract the sedative effect of butalbital.

Butalbital has a half-life of about 35 hours. Acetaminophen has a half-life of about 1.25 to 3 hours, but may be increased by liver damage and after an overdose. Caffeine has a half-life of about 5 to 7 hours.[4]

Formulation

Per most recent DEA Exemptions List ( http://www.deadiversion.usdoj.gov/schedules/exempt/exempt_rx_list.pdf) both old and new formulations of Fioricet are both exempt and not considered a controlled substance, not just the old formula. Per FDA guidelines[5] recommending that manufacturers limit the dose of acetaminophen in prescription products, the formulation of Fioricet has changed. "Old formulations"[6] of Fioricet contained 50 mg of butalbital, 325 mg of acetaminophen and 40 mg caffeine; "new formulations"[7] contain 50 mg of butalbital, 300 mg of acetaminophen and 40 mg caffeine. Manufacturers were allowed to make the "old formulation" of fioricet until January 1, 2014. Currently there is no move to remove or destroy the "old formulation", allowing for an odd situation in which there could be two different formulations of fioricet in pharmacies.

Formulation DEA Schedule Butalbital (mg) Acetaminophen (mg)Caffeine (mg)Form
Old Fioricetnone[6]50325[6]40tablet[6]
New FioricetCIII[7]50300[7]40capsule[7]

Confusion over control status

Confusion has arisen about the controlled substance status of this medication. Per DEA listing, Fioricet is a DEA exempt prescription product.[8] There is no logical rationale for why this is exempted from controlled substance scheduling, but it has been postulated that the concentration of butalbital with the acetaminophen (and caffeine) allows this to be an analgesic combination that the DEA allows exemption to. However peculiar it may be, Fioricet's sister product, Fiorinal, contains the same amount of butalbital per dose, combined with aspirin (and caffeine) instead of acetaminophen (and caffeine) but it is in fact a DEA Schedule III item.[9] However, Fioricet is listed as Schedule III in five states (MD, GA, UT, FL and NM).

Per the FDA National Drug Code Directory,[10] "new formulations" of Fioricet are listed as DEA Schedule III:

Labeller NDC DEA Schedule formstrength (Acetaminophen, Butalbital, Caffeine)note
Watson Pharma52544-080-01CIIIcapsule300 mg, 50 mg, 40 mgnew formulation
Rx Pak Division of McKesson65084-454-10CIIIcapsule300 mg, 50 mg, 40 mgnew formulation
Cardinal Health55154-3416-1nonetablet325 mg, 50 mg, 40 mgold formulation

Potential problems of two formulations

This change in designation affects mid-level providers, such as ARNPs and PAs, who are not allowed to prescribe controlled substances in some jurisdictions. Ostensibly, prescribers that are affected by this change could clearly indicate on the prescription that they would like the "old formulation" (perhaps by writing out the mg combination) until the "old formulation" is no longer available. Pharmacists dispensing or verifying this medication need to be keenly aware of the difference in formulation and CSA scheduling, as a misfill of the scheduled "new formulation" for the "old formulation" could have legal ramifications. Delays in verification and dispensing, or invalidation of a prescription due to a mid-level provider not having the ability to prescribe the controlled "newer formulation" could likewise affect patients through delays and hassles.

Variations

Name DEA Schedule Acetaminophen (mg)Aspirin (mg) Butalbital (mg) Caffeine (mg)Codeine (mg)LabellerFormEnd Marketing Date
Esgic[11][12]CIII3255040Forrest Laboratories, Inc[11][12]capsule,[11] tablet[12]
Esgic Plus[13][14][15]CIII5005040Forrest Laboratories, Inc;[13][14] A-S Medication Solutions LLC[15] capsule,[13] tablet[14][15]6/29/2014;[14][15] 8/10/2015[13]
Fioricet (new formulation)[7]CIII3005040Watson Pharma, Inc.[7] capsule
Fioricet (old formulation)[6]none3255040Cardinal Health[6] tablet1/1/2014
Fioricet (old formulation)[6]none3255040Qualitest[6] tablet
Fioricet with codeine[16]CIII300504030Watson Pharma, Inc.[16] capsule
Fiorinal[17]CIII3255040Watson Pharma, Inc.[17] capsule
Fiorinal with codeine[18]CIII325504030Watson Pharma, Inc.[18] capsule
Phrenilin[19] none32550Valeant Pharmaceuticals International[19] tablet
Phrenilin Forte[20]none65050Valeant Pharmaceuticals International[20] capsule
Phrenilin with caffeine and codeine[21]CIII325504030Valeant Pharmaceuticals North America[21] capsule

References

  1. ↑ Fioricet at RxList
  2. ↑ http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=4417
  3. ↑ A Hidden Cause of Headache Pain - New York Times
  4. ↑ http://www.webmd.com/balance/caffeine-myths-and-facts
  5. ↑ Food and Drug Administration. FDA drug safety communication: prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure.
  6. 1 2 3 4 5 6 7 8 (Old formulation) Fioricet package insert, Cardinal Health, Inc.
  7. 1 2 3 4 5 6 (New formulation) Fioricet package insert, Watson Pharma, Inc.
  8. ↑ http://www.deadiversion.usdoj.gov/schedules/exempt/exempt_rx_list.pdf
  9. ↑ http://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
  10. ↑ FDA National Drug Code Directory
  11. 1 2 3 Esgic tablet package insert, Forest Laboratories, Inc
  12. 1 2 3 Esgic capsule package insert, Forest Laboratories, Inc
  13. 1 2 3 4 Esgic Plus capsule package insert, Forest Laboratories, Inc
  14. 1 2 3 4 Esgic Plus tablet package insert, Forest Laboratories, Inc
  15. 1 2 3 4 Esgic Plus tablet package insert, A-S Medication Solutions LLC
  16. 1 2 Fioricet with codeine capsule package insert, Watson Pharma, Inc
  17. 1 2 Fiorinal capsule package insert, Watson Pharma, Inc
  18. 1 2 Fiorinal with codeine capsule package insert, Watson Pharma, Inc
  19. 1 2 Phrenilin tablet package insert, Valeant Pharmaceuticals North America
  20. 1 2 Phrenilin Forte capsule package insert, Valeant Pharmaceuticals International
  21. 1 2 Phrenilin (butalbital, acetaminophen, caffeine, and codeine phosphate) capsule package insert, Valeant Pharmaceuticals North America
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